We proposed to determine the primary structure of tryptophanyl-tRNA synthetase of Escherichia coli, to determine the relationship of its required thiol group to function of the enzyme, to determine the location of the required thiol group, and to crystallize the enzyme perhaps complexed to its cognate tRNATrp, for subsequent X-ray crystallography. The synthetase and its tRNA substrate are a model for other important protein-nucleic acid interactions. Tryptophanyl-tRNA synthetase of E. coli is a good choice for structure determination because the cognate enzyme in Bacillus stearothermophilus is the first aminoacyl-tRNA synthetase for which the primary sequence is known, because a superproducing strain of E. coli K12 is available, because the enzyme has a protomer of low molecular weight, and because pilot studies have shown the enzyme to be crystallizable. Moreover, the primary structures are known for E. coli, yeast, and mammalian tRNATrp. We have found a thiol peptide in the E. coli enzyme homologous to a thiol peptide in the human tryptophanyl-tRNA synthetase, and the E. coli enzyme is extensively homologous to the amino-terminal one-third of the B. stearothermophilus enzyme.